Investigative clinical therapeutic studies in children with acute leukemia, malignant lymphoma, histiocytosis X, and malignant solid tumors (brain tumors, neuroblastoma, Wilms' tumor, osteogenic sarcoma, Ewing's sarcoma, soft tissue sarcoma, and miscellaneous malignant neoplasms) are conducted in four areas: (a) Phase I coordinated studies of human pharmacologic and toxicologic aspects of new anticancer agents and new combinations and dosage regimens; (b) phase II systematic investigations of the effectiveness of individual anticancer agents or treatment programs in specific tumors; (c) Phase III comparative evaluations of selected drugs and/or therapy regimens; and (d) specific laboratory investigations in immunology and clinical pharmacology. The functioning cooperative group study mechanism is utilized to increase the size of the study populations and to shorten the duration of the study. Independent investigative probes are undertaken to explore leads resulting from or directed toward group studies. Several intergroup and national studies, ongoing and projected (National Wilms' Tumor Study, Intergroup Rhabdomyosarcoma Study, Intergroup Ewing's Sarcoma Study, Hepatoma Study, Hodgkin's Disease Study) are included. This research will be executed in an integrated multimodal manner. Attention to centralized data management will be given for the individual specialities of pediatrics, surgery, radiotherapy, pathology and laboratory support. Special attention will be given to clinical pharmacology and the immunological investigation required for optimal execution of current protocols employing high dose methotrexate or protocols requiring classification of lymphoid malignancies in order to establish proper therapy assignment.